The physical and biological processes governing the flow of blood are intimately responsible for safety and efficacy of all blood-wetted medical devices. The quest to design improved cardiovascular devices is however stifled by the inadequacies of current understanding of blood trauma and thrombosis. In spite of decades of experience with device design, hemotrauma research, and computational fluid dynamics modeling, it is virtually impossible to avoid deleterious hematological effects without experimental trail-and-error. Contemporary design relies upon venerable mathematical formula for blood that is more descriptive than predictive. Furthermore, we now understand that that these three phenomena are more closely coupled that previously appreciated. Indeed, previous models virtually neglected the existence of any coupling between these three processes. The objective of proposed project is to advance the accuracy and utility of a predictive model for thrombosis in blood-wetted cardiovascular devices. The research is built upon a combination of a previous model developed by the PI and colleagues for shear- mediated thrombosis and recent progress in modeling cellular-scale hemodynamics. Further incorporation of a model for synergy of platelet agonists is intended to yield a comprehensive design tool that is practical for design optimization of cardiovascular devices. Computer simulations will predict the dynamic interaction of red blood cells (RBCs) with platelets (Plts) in blood flow, and will rely upon a sophisticated theory of interacting continua that can predict the distribution of cells in any arbitrary flow path. The model will be validated and calibrated by both micro-scale computer simulations and microscopic visualization of blood cells in micro-channels. The predictive capacity of model will be demonstrated in three benchmark applications motivated by the development of cardiovascular devices for children: (1) parallel plate study incorporating various microscopic steps and crevices, (2) flow within blade tip of rotary blood pump, and (3) hydrodynamic bearing for pediatric rotary blood pump. Successful completion of these aims will produce a comprehensive computational model for blood trauma in cardiovascular devices, which we believe will contribute to the paradigm shift in the way these devices are developed: replacing trial-and-error with prescriptive bioengineering methods. Combined with computer optimization, the use of this model will greatly accelerate development of innovative new devices, and will reduce the occurrence of adverse complications. We also envision that the models will also be informative for diagnosing various clinical events, and help guide management of anticoagulation therapy.